Abstract

Background: Analysis of free light chains of immunoglobulins (FLC) in the serum is an effective method in the diagnosis of multiple myeloma. Plasma cells produce two types of FLC: κand λ-FLC. FLC, which are not incorporated into monoclonal intact immunoglobulins, are released into circulation, and then are filtered and reabsorbed in kidneys depending on their molecular weight. Circulating FLC commonly form homodimers, known as Bence-Jones protein, which is a biomarker of Bence-Jones multiple myeloma. According to the international guidelines, the ratio κ/λ FLC is an important diagnostic criterion of multiple myeloma. Aim: To evaluate the diagnostic and prognostic value of serum FLC in multiple myeloma patients. Materials and methods: We examined 118 patients with multiple myeloma, admitted to the Department of Hemoblastosis Chemotherapy of N.N. Blokhin Russian Cancer Research Center from 2010 to 2016, and 68 healthy men and women. Serum concentrations of FLC were measured with an immunoturbidimetric method using the test-system Freelite Human Lambda and Freelite Human Kappa (Binding Site Inc.). Results: The levels of monoclonal κor λ-FLC in patients with G-, A-myeloma and Bence-Jones multiple myeloma were significantly higher than those in the control group (p < 0.005). The diagnostic sensitivity of quantification of FLC and their ratio was 87.3% and 89.8%, and in combination with the use of immune electrophoresis it was close to 100%. Analysis of progression free survival and overall survival showed significant differences (p < 0.04) between the groups of patients according their κ/λ FLC ratio. The basal value of κ/λ FLC ratio of less than 0.04 and more than 140 was a predictor of unfavorable outcome . Conclusion : The inclusion of the determination of serum FLC into the assessment plan of patients with suspected monoclonal gammapathy makes it possible to increase diagnostic sensitivity of the available methods for paraprotein determination, as well as to monitor patients with non-secreting multiple myeloma. FLC analysis in multiple myeloma patients acquires special significance in the prognosis of remission, since the antitumor response based on their measurement is seen earlier than that based on the results of standard immunochemistry studies.

Highlights

  • in the serum is an effective method in the diagnosis of multiple myeloma

  • which are not incorporated into monoclonal intact immunoglobulins

  • in kidneys depending on their molecular weight

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Summary

Оригинальные статьи

Диагностика множественной миеломы до последнего времени основывалась на количественном определении циркулирующих моноклональных иммуноглобулинов. Парапротеин, секретируемый злокачественным клоном множественной миеломы, может быть представлен в виде молекул интактного иммуноглобулина, свободных легких цепей (СЛЦ), а также их сочетания. Плазматические клетки синтезируют пять изотипов тяжелых цепей и два типа легких – κ- и λ-СЛЦ, при этом клеток, продуцирующих κ-СЛЦ, в 2 раза больше. Нормальные и патологические плазматические клетки продуцируют больше легких цепей (до 40%), чем тяжелых, что позволяет обеспечить соответствующую конформацию молекул интактного иммуноглобулина в процессе их синтеза. СЛЦ продуцируются при всех типах множественной миеломы, в том числе у большинства больных. Разработка высокочувствительного автоматизированного метода определения СЛЦ в сыворотке крови на основе использования специфических антител к κ- и λ-СЛЦ сделала возможным внедрение этих показателей в клиническую практику [10, 11]. Цель настоящей работы – оценка диагностического и прогностического значения исследования СЛЦ в сыворотке крови больных множественной миеломой

Материал и методы
Тип миеломы
Findings
Background
Full Text
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